The recently discovered class of remarkably effective anti-HIV-1 natural products known as the calanolides are extremely difficult to obtain from natural sources. We herein propose a total synthesis of calanolide A, the most potent of the compounds reported. What is proposed is more than a natural product synthesis. It is necessary to develop an economical process for preparing significant quantities of the calanolides. A clinically successful compound in the series might eventually need to be synthesized in ton quantities to treat the large number of AIDS patients worldwide. Also a synthesis of calanolide A must allow for structural modification, since the intact natural product is very difficult to modify. this will lay the groundwork for the synthesis of analogues, which may be even more potent and exhibit fewer side effects than the parent natural product.